The objective of this project is to investigate extracellular matrix-cell interactions employing an experimental system of matrix-induced endochondral bone differentiation. This experimental model further affords a method to undertake systematic studies on the biochemistry and physiology of endochondral bone formation. Subjects currently under investigation are: (1) role of fibronectin during collagenous matrix-mesenchymal cell interaction; (2) immunofluorescent localization of fibronectin during matrix-induced cartilage, bone and bone marrow development; (3) changes in types I and III collagen synthesis during matrix-induced endochondral bone development; (4) appearance of gamma-carboxyglutamic acid during onset of mineralization during matrix-induced endochondral bone development; (5) synergistic action of growth hormone and thyroid stimulating hormone on endochondral bone differentiation; and (6) local influence of insulin on endochondral bone development.